Opioids Flashcards
Nociception-
“non conscious neural traffic due to (potential ) trauma to tissue.”
touch something hot, you pull your muscle away
Pain-
“complex, unpleasant awareness of sensation modified by experience, expectation, immediate context and culture”.
phantom pain, based on memories
steps of pain
- Nociceptors stimulated
- Release of Substance P and Glutamate
- Afferent nerve stimulated (a delta fibers- sharp pain, c fibers- unmyelated dull pain, travels slower, needs more stimulation)
- Fibres decussate
- Action potential ascends
- Synapse in thalamus
- Project to Post central gyrus
peripheral pain modulation
tissue damage sends inhibitory to s. gelatinous. rub it better by A beta fibers are activated, stimulate s. gelatinous, s. gelatinous sends inhibitory signals
central pain modulation
thalamus and cortex can stimulate periaqueductal grey matter, that sends inhibitory signals via endogenous opioids
Endogenous Opioids:
- Enkephalins
- Dynorphins
- B-endorphins
Opioid receptors
G protein receptors
• MOP/μ – most important clinically • DOP/δ • KOP/Κ
MOP receptor
found in brainstem and thalamus
responsible for therapeutic and adverse effects
GPCR: • Agonist binds • decrease in cAMP • Efflux of potassium • Hyperpolarisation of membrane • Decreases substance P and GABA release • Increases dopamine release, decreasing pain response
Phosphorylation and uncoupling causing opioid tolerance
opioid binds, decreased cAMP, intracellular Phosphorylation by kinases, this changes receptors, arresting can bind to receptor and displace the G protein, or opioid may not have the same effect as they can’t bind as well.
cAMP production causing opioid tolerance
opioids bind to receptor, decrease cAMP, when remove opioid, increased cAMP.
either decrease the time between doses, or increase each dose. neural excitability is caused by increased cAMP, causing withdrawal symptoms.
basics of opioids
- Exploit natural opioid receptors either agonise or antagonise
- Main therapeutic effects via μ-receptors
- Aim to modulate pain
- Also indicated in- cough, diarrhoea, palliation
morphine
• PO, IV, IM, SC, PR • Gut absorption erratic • Significant first pass effect- 40% oral bioavailability
• Rapidly enters all tissues including foetal, lipophilic • Struggles to cross blood- brain barrier, not protein bindings, not the best cos effects
elimination RENALLY
X^ morphine
Strong affinity to μ receptors., • Analgesia, Euphoria
#:• Respiratory Depression (main cause of death in OD) • Emesis • GI tract • Cardiovascular • Miosis • Histamine release- caution in asthmatics
X: renal impairment
fentanyl
- IV, Epidural, Intrathecal, Nasal • 80-100% bioavailability
- Highly lipophilic, highly protein bound • High level of CNS crossing
- Hepatic via CYP3A4
- Half life 6 minutes • Renally excreted
fentanyl, #X,
100x more potent than morphine, higher affinity for receptors, less histamine: sedation, constipation
action: analgesia, anaesthetic,
#• Respiratory Depression • Constipation • Vomiting
X: renal imp., less toxic than kidneys
codeine
PO, SC administration
• Codeine to Morphine via CYP2D6 • CYP2D6 inhibited by Fluoxetine(SSRI) • Variable expression
renal excretion
codeine potency, action, #
1/10th potency to morphine
mild-moderate analgesia, cough depressant
#: constipation, resp depression, worsen children
mixed agonist- antagonist example and metabolism
buprenorphine,
transdermal, buccal, sublingual, very lipophilic, hepatic metabolism via CYP3A4, biliary excretion, safe in renal imp. had life is long
buprenorphine potency, #, actions
very high affinity to receptor, long duration of action, not easily displaced, lower efficacy, action; moderate to severe pain, opioid replacement treatment #: • Respiratory depression • Low BP • Nausea • Dizziness
antagonist of opioids for OD
naloxone
IV, IM, intranasal, PO, low oral bioavailability, rapid onset of action
very lipophilic,
renal excreted
naloxone potency, action, #
• Greater affinity than morphine • Affinity less than buprenorphin Competitive antagonism of opioid, overdose treatment #: • Short half life • Slow infusion,
X opioids
special considerations:• Manual labourers/Drivers • Elderly • Bedbound • Asthmatics • Biliary tract obstruction • Respiratory Diseases • Renal impairment • Pregnancy
contraindication: • Hepatic failure • Acute respiratory Distress • Comatose • Head injuries • Raised ICP
Palliative prescribing
Buprenorphine, diamorphine, fentanyl, morphine and oxycodone
Indications: Pain, Shortness of breath • Manage side effects: nausea, constipation
• Months to Weeks
• Long acting background level of pain control
• Short acting top up doses for extra • Days to Hours
• Continuous subcut infusion
• Top up doses as needed
